When river water meets seawater: Insights into primary marine aerosol production

The impact of inorganic salts and organic matter (OM) on the production of primary marine aerosols is still under debate. To constrain their impact, we investigated primary aerosols generated by a sea-spray generator chamber using surface water samples from rivers, estuaries, and seas that were collected along salinity gradients in two temperate Korean coastal systems and one Arctic coastal system. Salinity values showed an increasing trend along the river-estuary-coastal water transition, indicating the lowest amount of inorganic salts in the river but the highest amount in the sea. In river samples, the lowest number concentration of primary aerosol particles (1.01 x 10(3) cm(-3)) was observed at the highest OM content, suggesting that low salinity controls aerosol production. Moreover, the number concentration of primary aerosols increased drastically in estuarine (1.13 x 10(4) cm(-3)) and seawater (1.35 x 10(4) cm(-3)) samples as the OM content decreased. Our results indicate that inorganic salts associated with increasing salinity play a much larger role than OM in aerosol production in river-dominated coastal systems. Laboratory studies using NaCl solution supported the conclusion that inorganic salt is a critical factor in modulating the particles produced from river water and seawater. Accordingly, this study highlights that inorganic salts are a critical factor in modulating the production of primary marine aerosols. (C) 2021 The Authors. Published by Elsevier B.V

Effects of

This study investigated the effects of Kudoa septempunctata genotype ST3 spores on ddY suckling mice. Purified Kudoa septempunctata spores were administered into the stomachs of the mice at 5 × 106 or 5 × 107 spores/mouse, with inactivated Kudoa (5 × 106 spores/mouse) or vehicle as controls. No abnormal clinical symptoms were observed and there were no variations in fluid accumulation ratio and cytokine gene expression in all groups. In addition, intact Kudoa spores and the 18S rDNA gene were only detected (by microscopy and quantitative PCR, respectively) in the groups administered such spores. This study thus confirms that spores from the ST3 strain of Kudoa septempunctata were excreted in the faeces without infecting the gastrointestinal tract in ddY suckling mice

Effects of Kudoa septempunctata genotype ST3 isolate from Korea on ddY suckling mice

This study investigated the effects of Kudoa septempunctata genotype ST3 spores on ddY suckling mice. Purified Kudoa septempunctata spores were administered into the stomachs of the mice at 5 × 106 or 5 × 107 spores/mouse, with inactivated Kudoa (5 × 106 spores/mouse) or vehicle as controls. No abnormal clinical symptoms were observed and there were no variations in fluid accumulation ratio and cytokine gene expression in all groups. In addition, intact Kudoa spores and the 18S rDNA gene were only detected (by microscopy and quantitative PCR, respectively) in the groups administered such spores. This study thus confirms that spores from the ST3 strain of Kudoa septempunctata were excreted in the faeces without infecting the gastrointestinal tract in ddY suckling mice

The Neomycin Resistance Cassette in the Targeted Allele of Shank3B Knock-Out Mice Has Potential Off-Target Effects to Produce an Unusual Shank3 Isoform

Variants of the SH3 and multiple ankyrin repeat domains 3 (SHANK3), which encodes postsynaptic scaffolds, are associated with brain disorders. The targeted alleles in a few Shank3 knock-out (KO) lines contain a neomycin resistance (Neo) cassette, which may perturb the normal expression of neighboring genes; however, this has not been investigated in detail. We previously reported an unexpected increase in the mRNA expression of Shank3 exons 1-12 in the brains of Shank3B KO mice generated by replacing Shank3 exons 13-16 with the Neo cassette. In this study, we confirmed that the increased Shank3 mRNA in Shank3B KO brains produced an unusual similar to 60 kDa Shank3 isoform (Shank3-N), which did not properly localize to the synaptic compartment. Functionally, Shank3-N overexpression altered the dendritic spine morphology in cultured neurons. Importantly, Shank3-N expression in Shank3B KO mice was not a compensatory response to a reduction of full-length Shank3 because expression was still detected in the brain after normalizing the level of full-length Shank3. Moreover, in another Shank3 KO line (Shank3 gKO) with a similar Shank3 exonal deletion as that in Shank3B KO mice but without a Neo cassette, the mRNA expression levels of Shank3 exons 1-12 were lower than those of wild-type mice and Shank3-N was not detected in the brain. In addition, the expression levels of genes neighboring Shank3 on chromosome 15 were altered in the striatum of Shank3B KO but not Shank3 gKO mice. These results suggest that the Neo cassette has potential off-target effects in Shank3B KO mice.11Nsciescopu

Artificial Intelligence-Powered Spatial Analysis of Tumor-Infiltrating Lymphocytes as Complementary Biomarker for Immune Checkpoint Inhibition in Non-Small-Cell Lung Cancer

PURPOSE Biomarkers on the basis of tumor-infiltrating lymphocytes (TIL) are potentially valuable in predicting the effectiveness of immune checkpoint inhibitors (ICI). However, clinical application remains challenging because of methodologic limitations and laborious process involved in spatial analysis of TIL distribution in whole-slide images (WSI). METHODS We have developed an artificial intelligence (AI)-powered WSI analyzer of TIL in the tumor microenvironment that can define three immune phenotypes (IPs): inflamed, immune-excluded, and immune-desert. These IPs were correlated with tumor response to ICI and survival in two independent cohorts of patients with advanced non-small-cell lung cancer (NSCLC). RESULTS Inflamed IP correlated with enrichment in local immune cytolytic activity, higher response rate, and prolonged progression-free survival compared with patients with immune-excluded or immune-desert phenotypes. At the WSI level, there was significant positive correlation between tumor proportion score (TPS) as determined by the AI model and control TPS analyzed by pathologists (P < .001). Overall, 44.0% of tumors were inflamed, 37.1% were immune-excluded, and 18.9% were immune-desert. Incidence of inflamed IP in patients with programmed death ligand-1 TPS at < 1%, 1%-49%, and >= 50% was 31.7%, 42.5%, and 56.8%, respectively. Median progression-free survival and overall survival were, respectively, 4.1 months and 24.8 months with inflamed IP, 2.2 months and 14.0 months with immune-excluded IP, and 2.4 months and 10.6 months with immune-desert IP. CONCLUSION The AI-powered spatial analysis of TIL correlated with tumor response and progression-free survival of ICI in advanced NSCLC. This is potentially a supplementary biomarker to TPS as determined by a pathologist.Y

Inflamed immune phenotype predicts favorable clinical outcomes of immune checkpoint inhibitor therapy across multiple cancer types

Background The inflamed immune phenotype (IIP), defined by enrichment of tumor-infiltrating lymphocytes (TILs) within intratumoral areas, is a promising tumor-agnostic biomarker of response to immune checkpoint inhibitor (ICI) therapy. However, it is challenging to define the IIP in an objective and reproducible manner during manual histopathologic examination. Here, we investigate artificial intelligence (AI)-based immune phenotypes capable of predicting ICI clinical outcomes in multiple solid tumor types.Methods Lunit SCOPE IO is a deep learning model which determines the immune phenotype of the tumor microenvironment based on TIL analysis. We evaluated the correlation between the IIP and ICI treatment outcomes in terms of objective response rates (ORR), progression-free survival (PFS), and overall survival (OS) in a cohort of 1,806 ICI-treated patients representing over 27 solid tumor types retrospectively collected from multiple institutions.Results We observed an overall IIP prevalence of 35.2% and significantly more favorable ORRs (26.3% vs 15.8%), PFS (median 5.3 vs 3.1 months, HR 0.68, 95% CI 0.61 to 0.76), and OS (median 25.3 vs 13.6 months, HR 0.66, 95% CI 0.57 to 0.75) after ICI therapy in IIP compared with non-IIP patients, respectively (p<0.001 for all comparisons). On subgroup analysis, the IIP was generally prognostic of favorable PFS across major patient subgroups, with the exception of the microsatellite unstable/mismatch repair deficient subgroup.Conclusion The AI-based IIP may represent a practical, affordable, clinically actionable, and tumor-agnostic biomarker prognostic of ICI therapy response across diverse tumor types